Gastrointestinal stasis, gastric hypersecretion, gastric dilation, nausea and emesis are observed routinely in patients that have suffered head injuries. These gastric symptoms are also observed following severe traumatic injury, and surgical procedures associated with extensive bleeding such as lung, heart and liver transplantation. There is a high degree of gastric feeding intolerance demonstrated by these patients, thus, they require aggressive total parenteral nutrition and occasionally invasive Gl surgical intervention for the maintenance of a positive energy and nitrogen balance. Additionally, there is a significant risk of aspiration that accompanies severe and prolonged gastric stasis such that intensive management of the airway is also required. Clearly, failure to regulate gastric function is a significant cause of post-trauma and post surgical morbidity and mortality. Although the association of gastric stasis with head trauma or surgery is axiomatic in the clinical literature, at this time, there are no explanations available which specifically and mechanistically connect the primary, and disparate, traumatic insults with the collapse of gastric function. Several recent, but unconnected observations, coupled with our studies on CNS control of gastric function, have led to the proposal of a unified hypothesis to explain why these apparently disparate traumatic insults can all produce a rapid and apparently autonomically-mediated failure to regulate gastric function: The serine protease thrombin (produced as a consequence of bleeding either within the cranium or in the periphery) can act directly upon protease-activated receptors [PARs] which exist in high density on neurons in the medullary dorsal vagal complex [DVC]. The DVC contains the neural circuitry responsible for autonomic control of the stomach, exists outside the blood-brain barrier, and is responsive to circulating metabolic products, peptides, and hormones. Thus, this PAR-DVC interaction may cause the disruption of vagal control of the stomach and manifest as gastric stasis with excessive acid secretion and/or retention. The proposed studies will examine the physiological validity of the hypothesis; the results will be used as a platform to launch a more detailed and mechanistic examination of the role of PARs in head trauma induced gastrointestinal stasis (i.e., via an R01 funding program).